Oxidant-mediated activation of phospholipase A2 in pulmonary endothelium

Exposure of bovine pulmonary arterial endothelial cells to the oxidant tert-butyl hydroperoxide caused a dose-dependent increase in the release of arachidonic acid and synthesis of the cyclooxygenase products, thromboxane, prostaglandin E2, prostaglandin D2, and prostacyclin

S. Chakraborti; G. H. Gurtner; J. R. Michael

2017

Scholarcy highlights

  • Exposure of bovine pulmonary arterial endothelial cells to the oxidant tert-butyl hydroperoxide caused a dose-dependent increase in the release ofarachidonic acid and synthesis of the cyclooxygenase products, thromboxane, prostaglandin E2, prostaglandin D2, and prostacyclin
  • There was no detectable production of peptide leukotrienes before or after administration of t-bu-OOH
  • Pretreatment with the oxygen radical scavenger 4-hydroxy-2,2,6,6-tetramethylpiperidino radical or the antioxidants vitamin E and dithiothreitol prevented the increased arachidonic acid release caused by t-bu-OOH. t-bu-OOH increased the activity of phospholipase A2 by increasing its apparent maximum velocity without affecting its Michaelis constant
  • The increased AA release caused by t-bu-OOH did not appear to require new RNA or protein synthesis, because pretreatment of the cells with actinomycin D or cycloheximide did not reduce the increased release of AA or activation of phospholipase A2 caused by t-bu-OOH
  • Dexamethasone pretreatment of the cells prevented the increase in phospholipase A2 activity, and AA release produced by t-bu-OOH. t-bu-OOH increased the activity of phospholipase A2 and release of AA in both the presence and absence of extracellular calcium
  • Treatment with calmodulin antagonists prevented the increased release of AA caused by t-bu-OOH
  • Division of Respiratory and Critical Care Medicine, Johns HopkinsMedical Institutions, Baltimore, Maryland 21205

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